Familial multiple cavernous malformation syndrome

Last revised by Henry Knipe on 21 Oct 2022

The familial multiple cavernous malformation syndrome, or familial cerebral cavernous malformation syndrome, is uncommon, accounting for only a minority of cavernous malformations.

It has been more frequently reported in patients of Hispanic descent 1.

The definition of familial multiple cavernous malformation syndrome is when there is one or more of the following 4,5:

  • multiple cerebral cavernous malformations

    • five or more cavernomas, or

    • one cavernoma and at least one other family member with one or more cavernomas

  • mutations in one of the three genes, KRIT1, CCM2 or PDCD10, which are associated with this disease

The presentation is most commonly with seizures (38-55%) 1 and focal neurological deficits, whilst recurrent large hemorrhages and headaches are less frequently encountered. 

Cutaneous lesions, including cherry hemangiomas and café au lait spots, are occasionally associated 6

In sporadic cases up to a 3rd of cavernous malformations are multiple. When familial the number of cavernomas is higher, typically five or more 1 and may be as high as dozens and dozens.

Familial cases usually have an autosomal dominant pattern of inheritance with incomplete penetrance 1,2

See: Zabramski classification of cerebral cavernomas.

The radiographic appearance of each cavernous malformation depends on size although in many instances individuals have innumerable lesions randomly distributed throughout the brain. 

For a discussion of the radiographic appearances see: cavernous malformations.

The differential is that of other causes of cerebral microhemorrhages, including 2:

MRI appearance may be mimicked by:

  • artificial heart valve metallic emboli (very rare)

  • pneumocephalus (very rare) 3

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Cases and figures

  • Case 1
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  • Case 2
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  • Case 3
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  • Case 4
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  • Case 5
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  • Case 6
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  • Case 7
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  • Case 8: intramedullary cavernoma
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